Is it possible to be overweight or obese and still be considered healthy? Most physicians advise their patients who are overweight or obese to lose weight because excess weight is a known risk factor for severe chronic diseases such as diabetes, high blood pressure or cardiovascular disease. However, in recent years, a controversy has arisen regarding the actual impact of increased weight on an individual’s life expectancy or risk of suffering from heart attacks. Some researchers argue that being overweight (body mass index between 25 and 30; calculate your body mass index here) or obese (body mass index greater than 30) primarily affects one’s metabolic health and it is the prolonged exposure to metabolic problems that in turn lead to cardiovascular disease or death.

According to this view, merely having excess weight is not dangerous. It only becomes a major problem if it causes metabolic problems such as high cholesterol levels, high blood sugar levels and diabetes or high blood pressure. This suggests that there is a weight/health spectrum which includes overweight or obese individuals with normal metabolic parameters who are not yet significantly impacted by the excess weight (“healthy overweight” and “healthy obesity”). The other end of the spectrum includes overweight and obese individuals who also have significant metabolic abnormalities due to the excess weight and these individuals are at a much higher risk for heart disease and death because of the metabolic problems.

Other researchers disagree with this view and propose that all excess weight is harmful, independent of whether the overweight or obese individuals have normal metabolic parameters. To resolve this controversy, researchers at the Mount Sinai Hospital and University of Toronto recently performed a meta-analysis and evaluated the data from major clinical studies comparing the mortality (risk of death) and heart disease (as defined by events such as heart attacks) in normal weight, overweight and obese individuals and grouping them by their metabolic health.

The study was recently published in the Annals of Internal Medicine (2014) as “Are Metabolically Healthy Overweight and Obesity Benign Conditions?: A Systematic Review and Meta-analysis” and provided data on six groups of individuals: 1) metabolically healthy and normal weight, 2) metabolically healthy and overweight, 3) metabolically healthy and obese, 4) metabolically unhealthy and normal weight, 5) metabolically unhealthy and overweight and 6) metabolically unhealthy and obese. The researchers could only include studies which had measured metabolic health (normal blood sugar, blood pressure, cholesterol, etc.) alongside with weight.

The first important finding was that metabolically healthy overweight individuals did NOT have a significantly higher risk of death and cardiovascular events when compared to metabolically healthy normal weight individuals. The researchers then analyzed the risk profile of the metabolically healthy obese individuals and found that their risk was 1.19-fold higher than the normal weight counterparts, but this slight increase in risk was not statistically significant. The confidence intervals were 0.98 to 1.38 and for this finding to be statistically significant, the lower confidence interval would have needed to be higher than 1.0 instead of 0.98.

The researchers then decided to exclude studies which did not provide at least 10 years of follow up data on the enrolled subjects. This new rule excluded studies which had shown no significant impact of obesity on survival. When the researchers now re-analyzed their data after the exclusions, they found that metabolically healthy obese individuals did have a statistically significant higher risk! Metabolically healthy obese subjects had a 1.24-fold higher risk, with a confidence interval of 1.02 to 1.55. The lower confidence interval was now a tick higher than the 1.0 threshold and thus statistically significant.

Another important finding was that among metabolically unhealthy individuals, all three groups (normal weight, overweight, obese) had a similar risk profile. Metabolically unhealthy normal weight subjects had a three-fold higher than metabolically healthy normal weight individuals. The metabolically unhealthy overweight and obese groups also had a roughly three—fold higher risk when compared to metabolically healthy counterparts. This means that metabolic parameters are far more important as predictors of cardiovascular health than just weight (compare the rather small 1.24-fold higher risk with the 3-fold higher risk).

Unfortunately, the authors of the study did not provide a comprehensive discussion of these findings. Instead, they conclude that there is no “healthy obesity” and suggest that all excess weight is bad, even if one is metabolically healthy. The discussion section of the paper glosses over the important finding that metabolically healthy overweight individuals do not have a higher risk. They also do not emphasize that even the purported effects of obesity in metabolically healthy individuals were only marginally significant. The editorial accompanying the paper is even more biased and carries the definitive title “ The Myth of Healthy Obesity”. “Myth” is a rather strong word considering the rather small impact of the individuals’ weight on their overall risk.

Some press reports also went along with the skewed interpretation presented by the study authors and the editorial.

“The message here is pretty clear,” said the lead author, Dr. Caroline K. Kramer, a researcher at the University of Toronto. “The results are very consistent. It’s not O.K. to be obese. There is no such thing as healthy obesity.”

Suggesting that the message is “pretty clear” is somewhat overreaching. One of the key problems with using this meta-analysis to reach definitive conclusions about “healthy overweight” or “healthy obesity” is that the study authors and editorial equate increased risk with unhealthy. Definitions of what constitutes “health” or “disease” should be based on scientific parameters (biomarkers in the blood, functional assessments of cardiovascular health, etc.) and not just on increased risk. Men have an increased risk of dying from cardiovascular disease than women. Does this mean that being a healthy man is a myth? Another major weakness of the study was that there was no data included on regular exercise. Numerous studies have shown that regular exercise reduces the risk of cardiovascular events. It is quite possible that the mild increase in cardiovascular risk in the metabolically healthy obese group may be due, in part, to lower levels of exercise.

This study does not prove that healthy obesity is a “myth”. Overweight individuals with normal metabolic health do not yet have a significant elevation in their cardiovascular risk. At this stage, one can indeed be “overweight” as defined by one’s body mass index but still be considered “healthy” as long as all the other metabolic parameters are within the normal ranges and one abides by the general health recommendations such as avoiding tobacco, exercising regularly. If an overweight person progresses to becoming obese, he or she may be at slightly higher risk for cardiovascular events even if their metabolic health remains intact. The important take-home message from this study is that while obesity itself can be a risk factor for increased risk of cardiovascular disease, it is far more important to ensure metabolic health by controlling cholesterol levels, blood pressure, preventing diabetes and important additional interventions such as encouraging regular exercise instead of just focusing on an individual’s weight.

Mammals have two types of fat tissue: Brown Adipose Tissue (BAT or “brown fat”) and White Adipose Tissue (WAT or “white fat”). Brown fat cells are packed with many small fat droplets and mitochondria, which is why they appear “brown” under the microscope. Their mitochondria contain high levels of the protein UCP-1 (uncoupling protein 1), which “uncouples” fat metabolism from the generation of chemical energy molecules (ATP) for the cell. Instead, brown fat cells release the energy contained in the fat in the form of heat. This explains why brown fat is primarily found in hibernating animals or in newborns that need to generate heat. They burn their fat to maintain their body temperature. White fat, on the other hand, cannot be burned off so easily and also seems to responsible for many of the deleterious effects associated with obesity, such as diabetes and inflammation.

Recent studies in humans have shown that even adult humans have small stores of brown fat, primarily located in the neck or near big blood vessels. Occasional small islands of brown fat cells can be found amid the large white fat tissue in the adult. Since brown fat is generally considered to be much healthier than white fat, scientists have tried to develop methods to convert white fat into brown fat. Some have used genetic approaches in mouse models of obesity, others have exposed human subjects to a few hours of cold temperatures. The paper “Increased cGMP promotes healthy expansion and browning of white adipose tissue” published in the FASEB Journal by Michaela Mitschke and colleagues (Online publication January 9, 2013) uses a rather unusual approach to induce the “browning” of white fat.

The researchers treated mice with Viagra (sildenafil), a drug that is normally used for erectile dysfunction. They found that only seven days of Viagra treatment increased the levels of the brown fat protein UCP-1 and that the white fat began showing the presence of “beige” (not quite white and not fully brown) fat. The choice of Viagra was not quite arbitrary, because they also showed that cultured fat cells contain cGMP-dependent protein kinase I (PKGI), which is part of the signaling pathway targeted by Viagra, and that increasing the levels of PKGI converted these cells into thermogenic brown fat cells. The researchers did not observe any weight loss in the mice, but they attributed this to the fact that they purposefully chose a very short treatment time in order to investigate fat conversion in the absence of fat loss. Their data suggests that longer treatment would lead to even more white-to-brown conversion of fat and to an actual weight loss, because the generated “beige” or brown-like fat cells could be easily burned off. A prior study that treated mice for 12 weeks with Viagra did indeed show some evidence of weight loss with Viagra treatment.

This new study is quite interesting and may have important practical implications because it uses an approved drug that is commonly available for human studies. Treating obese patients with Viagra would be much easier than trying to genetically convert their white fat to brown fat or to expose them to long periods of cold. However, overweight people should not expect that “Super-Size” orders at their favorite fast food joint will come with a Viagra pill. They also should not run to their physicians to ask for Viagra prescriptions at this point. One has to bear in mind that there are a number of caveats when trying to apply these findings in mice to humans. Chronic Viagra treatment in humans may be associated with some significant side effects and there is no consensus that “browning” of fat in adult humans will necessarily improve their health. Most of the data on the benefits of creating brown fat are based on animal studies. We therefore still need to await future studies, both in animals and in humans, that study the impact of long-term Viagra treatment on weight loss and associated health benefits as well as potential side effects, before definitive conclusions can be drawn. In the mean time, there will be plenty of opportunities to milk this research finding for humorous quips at late night talk shows.